Background: Given that 43-97% of preterm infants face postnatal growth restriction by hospital discharge, monitoring of growth is challenging but critical for clinical management of preterm infants. Currently, serial anthropometric measurements of weight and height are used to monitor growth but lack sensitivity. Thus, by the time significant deviations in growth trajectory are identified, an infant has already reached sub-optimal growth. A biomarker that is predictive of sub-optimal growth can serve as a preventative tool in clinical decision making. Blood urea nitrogen (BUN) may be one such potential metabolic biomarker, as it has been used as a measure of protein adequacy and thus, may additionally indicate quality of growth. While protein intake has a well-established correlation with growth, it is currently unknown if BUN is correlated with postnatal growth and if it can be used as a biomarker for growth.
Objectives: 1) to examine the relationship between BUN and macronutrient intake factors such as protein intake, protein-to-energy (P:E) ratios, and carbohydrate to non-protein energy (CHO:NPE %) to better understand BUN response; 2) to examine the potential of using BUN as a predictive metabolic biomarker of growth status in a multiple linear regression. We hypothesize that BUN will positively correlate with protein intake, P:E and negatively with CHO:NPE ratio. It will also be positively correlated with growth parameters: growth velocity, length gain, head circumference gain and fat free mass.
Methods: Very low birth weight preterm infants (n=101) born ≤30 weeks of gestation at McMaster Children’s Hospital’s level III NICU were included. BUN was assessed at three time points: baseline (SDay1), study day 14 (SDay14) and study day 21 (SDay21). Intake of protein and energy were collected for the 24-hour period prior to the BUN measure, their averages computed over SDay14 and SDay21 and included as confounding predictor variables. Other confounding variables such as maternal characteristics and baseline study group characteristics were also considered. Growth velocity, length gain and head circumference gain at SDay14 and SDay21, and body composition (FFM%, FFMI) between 36-40 weeks were examined as dependent growth variables. After an initial univariate analysis of baseline and maternal confounders, multiple linear regression models were then developed in a block design as follows: for the analysis of BUN vs macronutrient factors- block 1: 24-hour macronutrient intake factors + relevant baseline and/or maternal confounders; block 2: average macronutrient factors; for the analysis of BUN vs growth- block 3: BUN.
Results: In the analysis of BUN and macronutrient intake, BUN was found to have a significant positive correlation with P:E ratio at all time points. Protein intake was positively correlated with BUN only at SDay1 and SDay21. CHO:NPE ratio did not correlated with BUN at any time point. The R2 for the multiple regression of BUN and macronutrient factor analysis at SDay1, SDay14 and SDay21 was 0.19, 0.42 and 0.44 respectively. In the analysis of BUN vs growth, SDay1 BUN had a significant negative correlation with SDay21 growth velocity (p=0.02). The addition of SDay1 BUN to the model of SDay21 growth velocity was significant (p<0.01 of F change statistic, R2= 0.17). SDay21 BUN also had a significant negative correlation with SDay21 growth velocity (p<0.01) and its addition was significant to the model (p<0.01 of F change statistic, R2 =0.22). BUN was not related to SDay 14 growth velocity, or to length gain, head circumference gain or any body composition estimates at any time point. Additionally, P:E was found to be significantly negatively correlated with growth.
Conclusion: BUN is a statistically and clinically significant marker of nutritional adequacy, both of protein intake and energy in relation to protein intake. Addition of BUN adds to the explanation of variation in growth, and this is statistically significant, however, the additional variation explained may be too small to be clinically significant. Additionally, we observed that P:E ratio was significantly negatively correlated with growth. Thus, it may be more clinically pertinent to use high BUN values as a marker of inadequate energy to protein intake to prevent future sub-optimal growth.